Transcriptomic analysis of cognitive decline in ALS
The researchers in this study provided the first high-resolution transcriptomic atlas proving that cognitive decline in ALS is not caused by a single generalized pathological process, but rather by distinct, phenotype-specific cellular and regional defects.
The researchers mapped two distinct non-motor regions of the prefrontal cortex: Brodmann area 46 (BA46), which governs executive function, and Brodmann area 44/45 (Broca's area), which handles language production.
The authors show that pathological alterations are selectively concentrated within the deep layers of the dorsolateral prefrontal cortex (BA46) leading to localized synaptic dysfunction and a sharp reduction in mitochondrial metabolic activity.
Patients experiencing speech, fluency, and language deficits display a completely different structural profile that shifts the focus away from specific isolated neurons and is characterized by extensive glial-vascular dysregulation with highly reactive astrocytes, inflammatory microglia, altered endothelial cells, and compromised vascular-associated transcriptional programs.
https://sciencemission.com/executive-decline-in-amyotrophic-lateral-sclerosis
